"More chemo+XRT appears to be slightly better than more chemo alone, but not 8% better (strangely high, arbitrary number). I personally never would have hypothesized that it would be 10% better or something. Why it would have to be that much better is beyond me. The overall survival advantage of Herceptin in HER2+ breast patients is ~8%, but you'd be sued and drawn/quartered if you omitted that therapy. In this trial, 8% is the necessary hurdle to clear to even consider XRT? Weird."
5% events - 300,000
Editor or Editors: RICHARD T. HOPPE, M.D., FACR, FASTRO
Topic | SubTopic: Lymphoma / Leukemia | Adult Hodgkin's Disease
Article: Connors JM1, et al. ,Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma.
Longo DL1, et al. ,Progress in the Treatment of Hodgkin's Lymphoma.
The ECHELON-1 Trial was a pharma-sponsored trial testing the inclusion of brentuximab vedotin (an anti-CD30 drug conjugate) in an AVD backbone (ABVD minus bleomycin, because of potential pulmonary toxicity). So the trial was ABVD vs. BV-AVD. It included stage III-IV disease only. The primary end-point was “modified progression-free survival” (the time to progression, death, or non-complete response and use of subsequent anticancer therapy). So, if a patient had residual abnormality on a PET scan following treatment and the decision was made to consolidate with RT, this qualified as an event, even if the patient was subsequently progression-free.
The modified PFS at 2 years was 82% and 77%, for BV-AVD and ABVD, respectively, p=0.03. The 2-year OS rates were 97% and 95% (p=0.19). There were 18 deaths in the BV-AVD group (2.7%) and 22 on the ABVD group (3.2%). During treatment there were 9 deaths in the BV-AVD group, 7 due to neutropenia and infectious complications. 11 of 13 deaths in the ABVD group were from pulmonary toxicity.
The authors state, in conclusion that BV-AVD “appears to be more effective for the frontline treatment of advanced-stage classic Hodgkin’s lymphoma.”
In the accompanying editorial by Longo and DeVita, they praise this “advance,” stating that “the addition of brentuximab vedotin to AVD combination chemotherapy (supported with G-CSF to alleviate myelotoxicity) merits consideration as first-line treatment for advanced Hodgkin’s lymphoma.” At the same time, they manage to get in 2 “digs” against the use of RT in Hodgkin lymphoma, although RT was never an issue in this trial!
Some points to consider:
• The primary end-point has been challenged (modified PFS) as being appropriate.
• There are no survival differences. In trials of ABVD vs. ABVD + RT in early stage HL, PFS differences of 7% with the addition of RT (RAPID Trial) were considered inconsequential in the absence of an overall survival benefit!
• Patients who have an interim PET negative scan no longer have bleomycin included in cycles 3-6 (RATHL Trial), so in actual practice pulmonary toxicity and pulmonary deaths would be less for ABVD than was experienced in this trial.
• A conclusion of this trial is that growth factors should be employed with BV-AVD, but not needed with ABVD.
• Economic analysis. It’s promised. In an educational session at ASH the day prior to the presentation of these data and the publication in the NEJM, Nancy Bartlett, one of the co-authors presented an economic analysis. Cost of treatment with BV-AVD (including growth factors): $300,000. Cost of treatment with ABVD (growth factors not required): $4,000!
• Will this be practice changing? Will BV-AVD be accepted as standard? Hard to say at this point. This may be suitable for selected patients who are older and have existing pulmonary compromise. Marketing is likely to have an impact.
